The skin is a covering organ comprised of a plurality of layers (dermis, dermoepidermal junction, epidermis). The dermis is the tissue supporting the skin and is comprised of water, elastin fibers and collagen fibers (70% of dermal fibers), enveloped in an interstitial matrix of proteoglycans. Fibroblasts are the main cellular component of the dermis and are the source of collagen fiber and elastin fiber synthesis.
The outermost part is the epidermis, a multistratified epithelium consisting essentially of keratinocytes closely linked to one another. The basal layer of the epidermis is comprised of a layer of proliferative cells, primarily keratinocytes and melanocytes, which are anchored on the dermoepidermal junction (DEJ). The DEJ is an extracellular network structure that constitutes the interface between the dermis and the epidermis.
The skin, like all other organs, is subjected to the complex physiological process of aging. Intrinsic or chronological aging, which is the consequence of genetically programmed senescence, is distinguished from biochemical alterations due to endogenous factors. In the skin, it is characterized by a slowing of the regeneration of cells and extracellular matrices, leading to dermal and epidermal atrophy, dryness, a reduction in elasticity, and the appearance of fine lines and wrinkles.
Extrinsic aging is due to environmental stresses to which the body is subjected throughout life, such as pollution, sun, diseases, lifestyle habits, and so on. Its effects are combined with those of intrinsic aging in areas chronically exposed to the sun; this is referred to as photoaging. The main alterations associated with photoaging are located at the dermis and include: the appearance of pigment spots, a reduction and fragmentation of collagen fibers causing wrinkles and the accumulation of dystrophic elastic fibers constituting solar elastosis.
Numerous avenues of research have been explored to identify active agents capable of fighting cutaneous aging, among which are protection from environmental stresses (sun, pollution, etc.), activation of cell regeneration, and reinforcement of the extracellular collagen and elastin matrix. This research has led to the market release of numerous more or less effective active agents. Therefore, it remains important to identify new compounds capable of preventing or fighting cutaneous aging. The problem more specifically targeted by the invention is that of fighting the disorganization of fibrillar structures of the skin's extracellular matrix that appear during aging or photoaging.
The inventors recently identified a beneficial molecular target to fulfill this function. It is dermatopontin, a small acid protein, rich in tyrosine, abundant in the dermis and more specifically around the collagen fibers. It plays a key role in the structuring of collagen fibrils (Jonathan et al., J. Biol. Chem., 1993, vol. 268, pp. 19826-19832), participates in the process of adhesion of fibroblasts (Lewandowska et al., J. cell Sci., 1991, vol. 99, pp. 657-668), keratinocytes via integrin α3β1 and a proteoglycan-type receptor. These properties give dermatopontin an important role in healing (Akamoto et al., Biochem, 2010, vol. 49, pp. 147-155).
Confirming these results, the absence of dermatopontin in genetically modified mice results in a reduction in the thickness of the dermis and its collagen content, as well as in reduced elasticity of the skin (Takeda et al. J. Invest. Dermatol. 2002, vol. 119, pp. 678-683).
Independently of its structural role, dermatopontin can bind to decorin and TGF beta to form a trimeric complex and thus potentiate the action of TGF beta 1 (Okamoto et al., Biochem J. 1999 Feb. 1; 337 (3): 537-41).
The document JP2008-201777 discloses the use of peptides derived from dermatopontin, as agents promoting cell adhesion and healing.
The document US2005/0065089 discloses that native dermatopontin can be used to potentiate the activation of TGF beta in the context of a biological treatment of the disc herniations.
However, until now, no peptide according to the invention has been described for activating dermatopontin in the skin cells and preventing or repairing the skin signs of aging and photoaging.